全文获取类型
收费全文 | 399篇 |
免费 | 21篇 |
出版年
2023年 | 1篇 |
2022年 | 8篇 |
2021年 | 9篇 |
2020年 | 8篇 |
2019年 | 7篇 |
2018年 | 12篇 |
2017年 | 9篇 |
2016年 | 14篇 |
2015年 | 28篇 |
2014年 | 24篇 |
2013年 | 31篇 |
2012年 | 26篇 |
2011年 | 25篇 |
2010年 | 24篇 |
2009年 | 15篇 |
2008年 | 28篇 |
2007年 | 19篇 |
2006年 | 17篇 |
2005年 | 13篇 |
2004年 | 16篇 |
2003年 | 7篇 |
2002年 | 5篇 |
2001年 | 6篇 |
2000年 | 11篇 |
1999年 | 5篇 |
1998年 | 8篇 |
1997年 | 4篇 |
1996年 | 5篇 |
1994年 | 3篇 |
1993年 | 2篇 |
1992年 | 1篇 |
1991年 | 1篇 |
1990年 | 1篇 |
1989年 | 3篇 |
1986年 | 1篇 |
1985年 | 4篇 |
1983年 | 1篇 |
1982年 | 1篇 |
1981年 | 3篇 |
1980年 | 2篇 |
1979年 | 1篇 |
1977年 | 1篇 |
1975年 | 2篇 |
1968年 | 1篇 |
1966年 | 1篇 |
1964年 | 1篇 |
1963年 | 1篇 |
1962年 | 3篇 |
1887年 | 1篇 |
排序方式: 共有420条查询结果,搜索用时 15 毫秒
41.
Mariana Melissa Roque Claudio Baltazar Graa Cairrao Elisa 《Cellular and molecular neurobiology》2022,42(7):2289-2304
Cellular and Molecular Neurobiology - The Neurovascular Unit (NVU) is formed by vascular and neural cells controlling the cerebral hyperaemia. All the components are anatomically and functionally... 相似文献
42.
Miguel ángel Rubio Mauro Napolitano Jesús?A.?G. Ochoa?de?Alda Javier Santamaría-Gómez Carl J. Patterson Andrew W. Foster Roque Bru-Martínez Nigel J. Robinson Ignacio Luque 《Nucleic acids research》2015,43(20):9905-9917
Aminoacyl-tRNA synthetases (aaRSs) play a key role in deciphering the genetic message by producing charged tRNAs and are equipped with proofreading mechanisms to ensure correct pairing of tRNAs with their cognate amino acid. Duplicated aaRSs are very frequent in Nature, with 25,913 cases observed in 26,837 genomes. The oligomeric nature of many aaRSs raises the question of how the functioning and oligomerization of duplicated enzymes is organized. We characterized this issue in a model prokaryotic organism that expresses two different threonyl-tRNA synthetases, responsible for Thr-tRNAThr synthesis: one accurate and constitutively expressed (T1) and another (T2) with impaired proofreading activity that also generates mischarged Ser-tRNAThr. Low zinc promotes dissociation of dimeric T1 into monomers deprived of aminoacylation activity and simultaneous induction of T2, which is active for aminoacylation under low zinc. T2 either forms homodimers or heterodimerizes with T1 subunits that provide essential proofreading activity in trans. These findings evidence that in organisms with duplicated genes, cells can orchestrate the assemblage of aaRSs oligomers that meet the necessities of the cell in each situation. We propose that controlled oligomerization of duplicated aaRSs is an adaptive mechanism that can potentially be expanded to the plethora of organisms with duplicated oligomeric aaRSs. 相似文献
43.
Paulo FP Pimenta Alessandra S Orfano Ana C Bahia Ana PM Duarte Claudia M Ríos-Velásquez Fabrício F Melo Felipe AC Pessoa Giselle A Oliveira Keillen MM Campos Luis Martínez Villegas Nilton Barnabé Rodrigues Rafael Nacif-Pimenta Rejane C Sim?es Wuelton M Monteiro Rogerio Amino Yara M Traub-Cseko José BP Lima Maria GV Barbosa Marcus VG Lacerda Wanderli P Tadei Nágila FC Secundino 《Memórias do Instituto Oswaldo Cruz》2015,110(1):23-47
In the Americas, areas with a high risk of malaria transmission are mainly located in
the Amazon Forest, which extends across nine countries. One keystone step to
understanding the Plasmodium life cycle in Anopheles species from the Amazon Region
is to obtain experimentally infected mosquito vectors. Several attempts to colonise
Ano- pheles species have been conducted, but with only short-lived success or no
success at all. In this review, we review the literature on malaria transmission from
the perspective of its Amazon vectors. Currently, it is possible to develop
experimental Plasmodium vivax infection of the colonised and field-captured vectors
in laboratories located close to Amazonian endemic areas. We are also reviewing
studies related to the immune response to P. vivax infection of Anopheles aquasalis,
a coastal mosquito species. Finally, we discuss the importance of the modulation of
Plasmodium infection by the vector microbiota and also consider the anopheline
genomes. The establishment of experimental mosquito infections with Plasmodium
falciparum, Plasmodium yoelii and Plasmodium berghei parasites that could provide
interesting models for studying malaria in the Amazonian scenario is important.
Understanding the molecular mechanisms involved in the development of the parasites
in New World vectors is crucial in order to better determine the interaction process
and vectorial competence. 相似文献
44.
Maria C Anholeti Rodrigo C Duprat Maria R Figueiredo Maria AC Kaplan Marcelo Guerra Santos Marcelo S Gonzalez Norman A Ratcliffe Denise Feder Selma R Paiva Cicero B Mello 《Memórias do Instituto Oswaldo Cruz》2015,110(5):629-635
Studies evaluated the effects of hexanic extracts from the fruits and flowers
ofClusia fluminensis and the main component of the flower
extract, a purified benzophenone (clusianone), against Aedes
aegypti. The treatment of larvae with the crude fruit or flower extracts
from C. fluminensis did not affect the survival ofAe.
aegypti (50 mg/L), however, the flower extracts significantly delayed
development of Ae. aegypti. In contrast, the clusianone (50 mg/L) isolate from the
flower extract, representing 54.85% of this sample composition, showed a highly
significant inhibition of survival, killing 93.3% of the larvae and completely
blocking development of Ae. aegypti. The results showed, for the first time, high
activity of clusianone against Ae. aegypti that both killed and inhibited mosquito
development. Therefore, clusianone has potential for development as a biopesticide
for controlling insect vectors of tropical diseases. Future work will elucidate the
mode of action of clusianone isolated from C. fluminensis. 相似文献
45.
46.
Costa DL Carregaro V Lima-Júnior DS Silva NM Milanezi CM Cardoso CR Giudice  de Jesus AR Carvalho EM Almeida RP Silva JS 《PLoS neglected tropical diseases》2011,5(3):e965
Background
Leishmania braziliensis is the main causative agent of cutaneous leishmaniasis in Brazil. Protection against infection is related to development of Th1 responses, but the mechanisms that mediate susceptibility are still poorly understood. Murine models have been the most important tools in understanding the immunopathogenesis of L. major infection and have shown that Th2 responses favor parasite survival. In contrast, L. braziliensis–infected mice develop strong Th1 responses and easily resolve the infection, thus making the study of factors affecting susceptibility to this parasite difficult.Methodology/Principal Findings
Here, we describe an experimental model for the evaluation of the mechanisms mediating susceptibility to L. braziliensis infection. BALB/c mice were inoculated with stationary phase promastigotes of L. braziliensis, isolates LTCP393(R) and LTCP15171(S), which are resistant and susceptible to antimony and nitric oxide (NO), respectively. Mice inoculated with LTCP393(R) presented larger lesions that healed more slowly and contained higher parasite loads than lesions caused by LTCP15171(S). Inflammatory infiltrates in the lesions and production of IFN-γ, TNF-α, IL-10 and TGF-β were similar in mice inoculated with either isolate, indicating that these factors did not contribute to the different disease manifestations observed. In contrast, IL-4 production was strongly increased in LTCP393(R)-inoculated animals and also arginase I (Arg I) expression. Moreover, anti-IL-4 monoclonal antibody (mAb) treatment resulted in decreased lesion thickness and parasite burden in animals inoculated with LTCP393(R), but not in those inoculated with LTCP15171(S).Conclusion/Significance
We conclude that the ability of L. braziliensis isolates to induce Th2 responses affects the susceptibility to infection with these isolates and contributes to the increased virulence and severity of disease associated with them. Since these data reflect what happens in human infection, this model could be useful to study the pathogenesis of the L. braziliensis infection, as well as to design new strategies of therapeutic intervention. 相似文献47.
Galaz-Vega R Hernández-Kelly LC Méndez JA Cisneros B Ortega A 《Neurochemical research》2005,30(2):237-243
Glial glutamate receptors are likely to be involved in neuronal differentiation, migration, and plasticity. Dystrophin, the protein defective in Duchenne muscular dystrophy (DMD) is widely expressed in the Central Nervous System. Activation of internal promoters of the DMD gene leads to the production of several proteins, the Dystrophin-71 (Dp-71) being the most abundant in the encephalon. This protein is known to stabilize neurotransmitter receptors in clusters and its absence has been correlated with cognitive deficits in a mouse model. Using cultured chick Bergmann glia cells and mouse cerebellar fusiform astrocytes, we demonstrate here that glutamate receptor activation results in a time and dose dependent decrease of Dp-71 levels. This effect is mediated through
amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors. The present results suggest an involvement of Dp-71 in glutamate receptor signaling and possibly clustering and further support the notion of an active role of glia in the physiology of glutamatergic transmission. 相似文献
48.
Thrichomys apereoides, a caviomorph rodent species common in a highly endemic area for Chagas disease in Brazil, may act as reservoir of the parasite. However, no information is available concerning its sibling species Thrichomys pachyurus, found in the Pantanal region, where Trypanosoma cruzi is found only in the enzootic cycle. We followed up the cross infection of these cryptic species with two isolates derived from naturally infected T. pachyurus and Thrichomys apereoides laurentius. No regional co-adaptation between Thrichomys species and the regional isolates were noticed. However, significant differences in the outcome of the infection were observed. T. a. laurentius was more resistant than T. pachyurus, as expressed by lower parasitemia and less histopathological damage. The routine biochemical markers used for laboratory rodents were unsuitable for follow up of infection in Thrichomys spp, since they did not correlate with the histopathological findings or allowed the kinetic follow-up of tissue colonization by the parasite. 相似文献
49.
Affinity chromatography represents a promising technique for decoding the proteomics universe. While conventional affinity purification is being used in conjunction with two-dimensional electrophoresis (2D-PAGE) and mass spectrometry (MS) for the study of proteomes and subproteomes, scientists are still confronted with the need for specific and tailor-made affinity ligands to target desired groups and families of proteins. Evidence has shown that, in many situations, synthetic affinity ligands can circumvent inconveniences associated with the utilisation of biological ligands for the chromatography-based purification of biomolecules. This review will highlight the potential applications of affinity chromatography and synthetic de novo designed ligands as separation tools for proteomics. 相似文献
50.
The protein surface is the interface through which a protein molecule senses the external world. The composition of this interface, in charged, polar and/or hydrophobic residues is crucial for both the activity and stability of the protein. Protein immobilization on surfaces has been extensively explored as one of the most effective approaches for stabilization. The mechanism of stabilization, however, is still poorly understood, and usually the success of any method is more a matter of trial and error rather than the result of rational concepts. The importance of local unfolding processes in a number of biologically significant processes has been recognized and attracted increasing attention. Unfolding regions have been localized in different proteins including the recombinant cutinase from Fusarium solani pisi. The study of three structural surface regions associated with early cutinase unfolding events was the basis for the approach followed in this work. A 64-member solid-phase combinatorial library of ligands was synthesized on a triazine-substituted agarose matrix using a modified 'mix and split' procedure. The combinatorial library was assessed for binding to cutinase from Fusarium solani pisi in a biologically active form. Four lead ligands (3/5, 3/7, 4/5, 4/7) have been selected in which immobilized cutinase presented a relative activity of 30-60% as compared to the free enzyme. 相似文献